Skin care actives, for example the Vitamin B compound, niacinamide, are well known cosmetic skin care agents that are believed to provide a variety of skin care benefits (see, e.g., Bissett el al. “Niacinamide: A B Vitamin that Improves Aging Facial Skin Appearance” and Draelos “Clinical Situations Conducive to Proactive Skin Health and Anti-Aging Improvement”). Some of the reported benefits include improvement in the appearance of facial skin texture, red blotchiness, hyperpigmentation, and the enhancement of skin barrier function. Given these benefits, there is a continuing desire to increase the amount of vitamin B compounds delivered into human skin from topically applied cosmetic compositions to further enhance the skin benefits provided by these compounds. There is also a desire to ensure the skin care active has sufficient time to act on the skin.
It is known that a rate limiting step in the percutaneous absorption of ingredients is their initial penetration into and across the stratum corneum, see, e.g., Suhonen et al., “Chemical Enhancement of Percutaneous Absorption In Relation To Stratum Corneum Structural Alterations”, Suhonen et al., Journal of Controlled Release, 59 (1999), pgs 149-161. Suhohen et al. also observed that there are at least two potential pathways through the stratum cornenum: 1) transcellular (i.e., across the corneocytes and the lipid matrix), and 2) intercellular (i.e., via the lipid domains between the corneocytes), with the intercellular route believed to be providing the principal route for the permeation of ingredients.
Skin penetration enhancers are well known. As far back as 1997, a literature review by Osborne et al. purported to find more than 275 chemical compounds cited as enhancing skin permeation (see, e.g., Osborne, David, “Skin Penetration Enhancers Cited in the Technical Literature, Pharmaceutical Technology”, 1997, pp 58-66). Compounds identified by Osborne include various species of fatty alcohols, fatty acid esters, fatty acids, fatty alcohol ethers, enzymes, amines and amides, surfactants, n-methyl pyrrolidones, ionic compounds and various others. More recently, Williams et al. noted that “[n]umerous compounds have been evaluated for penetration enhancing activity, including sulphoxides (such as dimethylsulphoxide, DMSO), azones (e.g., laurocapram), pyrrolidones, (for example 2-pyrrolidone, 2P), alcohols and alkanols (ethanol, or decanol), glycols (for example propylene glycol, PG, a common excipient in topically applied dosage forms), surfactants (also common in dosage forms) and terpenes”. Williams et al., “Penetration Enhancers”, Advanced Drug Delivery Reviews 56, pgs 603-618 (2004), see also, Pathan et al., “Chemical Penetration Enhancers for Transdermal Drug Delivery Systems”, Tropical Journal of Pharmaceutical Research, Vol. 8(2), pgs 173-179 (2009).
U.S. patent application Ser. No. 13/803,692 discloses use of the penetration enhancer hexyldecanol in combination with glycerin and a vitamin B active. Glycerin is known to be an important component of skin hydration in topical applications. Niacinamide, which is a vitamin B compound soluble in both water and glycerin, is associated with a variety of cosmetic skin care benefits. Given the cosmetic benefits provided by glycerin and vitamin B compounds, it is often desirable to combine both in cosmetic/skin care compositions. However, it has been observed that the presence of glycerin in such a cosmetic composition can retard the penetration of niacinamide into the skin, when measured over a 6 hour time period. The inventors of U.S. Ser. No. 13/803,692 have surprisingly discovered that introducing a penetration enhancer, e.g. hexyldecanol or other diol, may counteract this effect and, in some instances, enables glycerin to synergistically enhance rather than retard penetration of niacinamide into the stratum corneum.
While various skin penetration enhancers are known, their mechanisms of action, particularly in the stratum corneum, are still being investigated. For example, Suhonen et al. postulated that “many penetration enhancers are capable of inserting between the hydrophobic tails of the bilayer, thus disturbing their packing, increasing their fluidity and, subsequently, leading to easier diffusion of lipid-like penetrants”. Suhonen et al. also concluded however that “[a]lthough during the last 10 years an enormous amount of knowledge became available on the structure of the stratum corneum and the effect of solvent and penetration enhancers on this structure, still our knowledge on this tissue and its lipid organization is very limited”. Similarly, Williams et al. noted in 2004 that the inclusion of penetration enhancers “into topical or transdermal formulations is limited since the underlying mechanisms of action of these agents are seldom clearly defined”. Even more recently, Williams and Barry, “Penetration enhancers”, Advanced Drug Delivery Reviews, Vol. 64, pgs 128-137 (2012), stated that “[i]t is difficult to select rationally a penetration enhancer for a given permeant.” While the effects of certain individual ingredients on skin penetration has been studied to some degree, the role that these ingredients, or combinations of ingredients, may play in penetration of cosmetic agents through the stratum corneum appears to be less studied or defined.